GCKR and PPP1R3B identified as genome-wide significant loci for plasma lactate: the Atherosclerosis Risk in Communities (ARIC) study

A. Tin, P. Balakrishnan, T. H. Beaty, E. Boerwinkle, R. C. Hoogeveen, J. H. Young, W. H.L. Kao

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: To investigate the genetic influence of circulating lactate level, a marker of oxidative capacity associated with diabetes. Methods: We conducted a genome-wide association study of log-transformed plasma lactate levels in 6901 European-American participants in the Atherosclerosis Risk in Communities study. For regions that achieved genome-wide significance in European-American participants, we conducted candidate region analysis in African-American subjects and tested for interaction between metformin use and the index single nucleotide polymorphisms for plasma lactate in European-American subjects. Results: The genome-wide association study in European-American subjects identified two genome-wide significant loci, GCKR (rs1260326, T allele β=0.08; P=1.8×10-47) and PPP1R3B/LOC157273 (rs9987289, A allele β=0.06; P=1.6×10-9). The index single nucleotide polymorphisms in these two loci explain 3.3% of the variance in log-transformed plasma lactate levels among the European-American subjects. In the African-American subjects, based on a region-significant threshold, the index single nucleotide polymorphism at GCKR was associated with plasma lactate but that at PPP1R3B/LOC157273 was not. Metformin use appeared to strengthen the association between the index single nucleotide polymorphism at PPP1R3B/LOC157273 and plasma lactate in European-American subjects (P for interaction=0.01). Conclusions: We identified GCKR and PPP1R3B/LOC157273 as two genome-wide significant loci of plasma lactate. Both loci are associated with other diabetes-related phenotypes. These findings increase our understanding of the genetic control of lactate metabolism.

Original languageEnglish (US)
Pages (from-to)968-975
Number of pages8
JournalDiabetic Medicine
Volume33
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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